SPECIFIC-ENZYME RELEASE OF CELLULOSE-BOUND DRUGS, EXPERIMENTAL AND THEORETICAL-STUDY
SPECIFIC-ENZYME RELEASE OF CELLULOSE-BOUND DRUGS, EXPERIMENTAL AND THEORETICAL-STUDY
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DOI：
10.1002/app.1986.070320101
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发表时间：
1986-07-01
影响因子：
3
通讯作者：
DELLACHERIE, E
中科院分区：
文献类型：
--
作者：
LAPICQUE, F;DELLACHERIE, E
通过将羟基药物的底物酯共价连接至纤维素衍生物来制备福尔可定的各种聚合物前药。选择药物的酯衍生物，使得所得不溶性纤维素前药成为α-胰凝乳蛋白酶的底物。在模拟肠道介质的条件下，研究了各种间隔臂的此类化合物的水解。开发了一个理论模型来描述这种水解的酶催化，考虑到吸附的聚合物上的酶，水解反应，和酶变性。所得到的方程使用独立确定的参数值，如朗缪尔吸附常数，酶的变性常数，和初始水解速率常数成功地与实验数据相关。
Various polymeric prodrugs of pholcodine were prepared by covalently linking a substrate ester of the hydroxylic drug to cellulosic derivatives. The ester derivatives of the drug were chosen so that the resulting insoluble cellulosic prodrugs became substrates of α‐chymotrypsin. The hydrolysis of such compounds was studied for various spacer arms in conditions simulating the intestinal medium. A theoretical model was developed to describe the enzymatic catalysis of this hydrolysis, taking into account the adsorption of the enzyme onto the polymer, the hydrolysis reaction, and the enzyme denaturation. The resulting equations using independently determined parameter values such as the Langmuir adsorption constants, the enzyme denaturation constants, and the initial hydrolysis rate constant successfully correlated with the experimental data.